Reactions to Remicade Are Rare

Canadian real-world study confirms infliximab safety

Action Points

The real-world incidence of infusion reactions to infliximab, an antibody targeting TNF-a in inflammatory diseases, is low and reactions are overwhelming mild or moderate.

The incidence of infusion reactions is highest in the first year of treatment and decreases yearly thereafter.

The incidence of reactions to infusion of infliximab in a real-world setting is low. In fact, the incidence observed in a Canadian registry was lower than that reported in cohort studies, say Canadian researchers.

The incidence of infusion reactions in the registry, known as RemiTRAC, was 1.3%, compared with a rate of 2.5% to 6.1% in other cohort studies, the investigators reported in The Journal of Rheumatology.

"One reason may be that RemiTRAC Infusion is a long-term registry that was ongoing for 7 years," they wrote. "Our data show that about two-thirds of infusion reactions were observed during the first year of therapy and the mean number of infusions per patients was about 15, representing over 2 years of exposure. Other studies, and all randomized controlled trials, had a much shorter observation period."

Led by Denis Choquette at the Institut de Rheumatologie de Montréal, researchers assessed the rate of infliximab infusion reactions and factors associated with infusion reactions among 1,632 patients participating in RemiTRAC, in whom 24,852 infusions were recorded. Total follow-up was 3,427.1 patient-years. Each patient received a mean of 15.3 infusions.

Most patients in the registry were treated for rheumatologic conditions, such as rheumatoid arthritis (RA, 40.1%), ankylosing spondylitis (AS, 17.5%) and psoriatic arthritis (PsA, 5.5%). Others received infusions for the treatment of diseases such as Crohn Disease, ulcerative colitis (UC), and plaque psoriasis (PSO). RA patients in RemiTRAC were mostly women (72.5%), while 73.8% of the patients with AS were men.

Prophylactic premedication use varied by indication, to slightly more than 40% of infusions administered to patients with a rheumatologic condition, with acetaminophen being the most common premedication. Premedication was prescribed in about two thirds of infusions of patients with inflammatory bowel disease, and IV steroids were used >50% of the time. Patients with PSO were premedicated for 53% of their infusions.

A total of 322 infusions were associated with an infusion reaction, for an overall incidence of 1.3%. Some 12.3% of patients experienced at least one infusion reaction.

Of the 322 infusion reactions, 154 were classified as mild, 152 as moderate, and 16 (5%) were severe. Twenty-six infusion-related adverse events led to discontinuation of infliximab.

Four infusion reactions were serious: a moderate temperature increase, itching/flushing that required hospitalization), chest pain/flushing, and moderate chest pain alone; the latter two reactions occurred in the same patient but 3 months apart. None of the four required discontinuation.

In those who were infliximab-naïve prior to entry, the infusion reaction incidence was 1.5%. In contrast, the rate was 0.98% in patients who had received infliximab infusions previously.

The incidence of infusion reactions was 2.1% at infusion number 1, varied from 1.8% to 3.2% between infusions number 2 and 8 (corresponding to year 1 of treatment) and dropped to <2% after the first year of treatment.

The most common infusion adverse event was pruritus, which occurred in 19.9% of infusion reactions. Other common infusion adverse events were flushing (9.9%), dyspnea (6.2%), nausea (4.7%), urticaria (4.7%) and headaches (4.0%).

As a management approach to infusion reactions, antihistamines or steroids were used in 54.97% and 22.05% of infusion reactions, respectively. After an infusion reaction, the most common courses of action were to slow (36.65%) and/or stop (66.77%) the infusion of infliximab and infuse normal saline (70.81%). "Both of these strategies appeared successful because the infusion of infliximab was restarted in 75.8% of cases where it had been stopped, and the infusion rate was re-increased in 85.7% of cases where it had been slowed," the investigators wrote.

In a multivariate model, the use of antihistamines as pretreatment (2.49% versus 1.32% if not used, P<0.0001), the number of previous infusion reactions (odds ratio [OR] 2.04, 95% CI 1.78-2.34, P<0.0001), the time since the most recent infusion (OR 0.99, 95% CI 0.99–1.00, P<0.0006), female sex (2.21% versus 1.49% for males, P<0.0001) and the use of corticosteroids at enrollment in patients with previous infliximab infusions (2.98% versus 1.20%, P<0.002) were significantly associated with an increased incidence of infusion reactions.

The incidence of infusion reaction decreased with each passing year (OR 0.68, 95% CI 0.63–0.73, P<0.0001). The authors speculate that "the year of administration is likely a surrogate of the site's experience and comfort level with the infusions," adding that the reduction in infusion reactions over time could "reflect improved experience of the sites or maybe less frequent reporting of insignificant infusion reactions."

"After reviewing the data, there was a consensus among the investigators that, considering the low incidence of infusion reaction, no premedication is recommended," they advise. "Once an infusion reaction has occurred, premedication could be considered and tailored to the type of infusion reaction prior to the next infusion."

Limitations are the risk for selection biases inherent in observational studies. Also, because infusion reactions were recorded only if they occurred within 24 hours, delayed reactions would be missed by the analysis.

The study was supported and conducted by Janssen. One author is an employee of the company.

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